Mild exercise plus levothyroxine ameliorate deficits of spatial navigation, anxiety profile, and hippocampal BDNF in hypothyroid male offspring rats.

PURPOSE: Levothyroxine (LEV) monotherapy cannot completely improve cognitive and behavioral impairments induced by hypothyroidism, whereas a combination therapy of exercise and LEV may ameliorate these deficits. This study aimed to determine the effects of mild-intensity forced exercise and LEV treatment on the anxiety profile and cognitive functions in male offspring of hypothyroid dams. METHOD: Twenty-four female rats (mothers) were randomly divided into sham (healthy) and hypothyroidism groups and then placed with male rats to mate. The presence of vaginal plaque confirmed pregnancy (gestational day, GD 0). 6-propyl-2-thiouracil (PTU, 100 ppm) was added to the drinking water of the hypothyroidism group from GD 6 to the 21st postnatal day (PND). The sham group received tap water. On PND 21, serum T4 levels of mothers, and 10 pups were measured to confirm hypothyroidism. Sixty-four male pups were left undisturbed for 30 days and then were divided into eight groups that received saline or LEV (50 µg/kg, i.p.) with or without forced mild-intensity exercise. After 14 days of interventions, anxiety-like behaviors, spatial learning and memory, and hippocampal brain-derived neurotrophic factor (BDNF) levels were evaluated. FINDING: A pre and postnatal PTU-induced model of hypothyroidism increased anxiety-like behaviors, impaired spatial learning and memory, and decreased hippocampal BDNF levels in male offspring rats. LEV alone increased BDNF levels and improved spatial learning. Exercise alone increased BDNF levels, improved spatial learning and memory, and decreased anxiety-like behaviors. Exercise plus LEV more effectively improved anxiety-like behaviors and spatial learning than exercise or LEV alone. CONCLUSION: Practically, these pre-clinical findings highlight the importance of the combination of exercise and LEV regimen in treating patients with hyperthyroidism.

Risk of congenital anomalies associated with antithyroid treatment during pregnancy: a meta-analysis

To evaluate the association of either propylthiouracil or methimazole treatment for hyperthyroidism during pregnancy with congenital malformations, relevant studies were identified by searching Medline, PubMed, the Cochrane Library and EMBASE. We intended to include randomized controlled trials, but no such trials were identified. Thus, we included cohort studies and case-control studies in this meta-analysis. A total of 7 studies were included in the meta-analyses. The results revealed an increased risk of birth defects among the group of pregnant women with hyperthyroidism treated with methimazole compared with the control group (odds ratio 1.76, 95% confidence interval 1.47-2.10) or the non-exposed group (odds ratio 1.71, 95% confidence interval 1.39-2.10). A maternal shift between methimazole and propylthiouracil was associated with an increased odds ratio of birth defects (odds ratio 1.88, 95% confidence interval 1.27-2.77). An equal risk of birth defects was observed between the group of pregnant women with hyperthyroidism treated with propylthiouracil and the non-exposed group (odds ratio 1.18, 95% confidence interval 0.97-1.42). There was only a slight trend towards an increased risk of congenital malformations in infants whose mothers were treated with propylthiouracil compared with in infants whose mothers were healthy controls (odds ratio 1.29, 95% confidence interval 1.07-1.55). The children of women receiving methimazole treatment showed an increased risk of adverse fetal outcomes relative to those of mothers receiving propylthiouracil treatment. We found that propylthiouracil was a safer choice for treating pregnant women with hyperthyroidism according to the risk of birth defects but that a shift between methimazole and propylthiouracil failed to provide protection against birth defects. .

Model of induction of thyroid dysfunctions in adult female mice

It is described the elaboration of a protocol to induce hyperthyroidism and hypothyroidism in mice by administrating thyroxin and propylthiouracil, respectively, in the drinking water. The drugs were administered to adult female mice of the Swiss strain for 30 days in order to obtain a systemic status of thyroid dysfunction. The induction of hyperthyroidism and hypothyroidism in the animals was confirmed by the histomorphological analysis of the thyroid in the end of the experiment, when the state of gland dysfunction in the animals submitted to the treatment was observed

Descreve-se a elaboração de um novo protocolo de indução ao hipertireoidismo e hipotireoidismo em camundongos, por meio da administração de tiroxina e propiltiouracil, respectivamente, na água de beber. As drogas foram administradas a camundongos fêmeas adultas Swiss por 30 dias para obtenção das disfunções tireoidianas sistêmicas. A indução de hipertireoidismo e hipotireoidismo nos animais foi confirmada pela análise histomorfológica e histomorfométrica da glândula tireoidiana ao final do experimento, quando observou-se o estado de disfunção glandular nos animais submetidos ao tratamento

Effect of Thyroxine and Propylthiouracil in Ehrlich Ascitic Tumor Cells / Efecto de la Tiroxina y Propiltiouracilo en las Células del Tumor Ascítico de Ehrlich

The main purpose of this study was to investigate the effect of thyroxine and PTU in ascitic Ehrlich tumor cells. Tumor was implanted in 30 female mice distributed in three groups: treated with PTU, treated with thyroxine and control. Each group received an intraperitoneal injection of neoplastic cells, pre-incubated with sterile solutions of PTU, thyroxine and distilled water, respectively. On the fifth and seventh days after inoculation, animals received an intraperitoneal injection of the respective solutions. On the tenth day after inoculation, animals were sacrificed. Volume of ascitic liquid, number of neoplastic cells/ml and percentage of viable cells were determined. Ascitic liquid smears were carried out for tumor cytological evaluation. There was no difference among groups regarding ascitic liquid and as for the number and viability of tumor cells. However, cells under the effect of thyroxine presented significantly larger mean of nuclear diameter, size and number of nucleolus organizer regions. In this group, there was a predominance of clear, round cells with abundant eosinophilic and very vacuolated cytoplasm with little defined edges. Under the PTU effect, tumor cells were small with hyperchromatic nucleus and the same number of NORs as the control group. It was concluded that PTU and thyroxine have not changed the number and viability of cells after 10 days of tumor inoculation but they changed significantly cell characteristics. Whilst thyroxine increases cell size and the number of NORs of ascitic Ehrlich tumor cells, PTU causes an opposite effect.

El propósito principal de este estudio ha sido investigar el efecto de la tiroxina y del propiltiouracilo (PTU) en las células del tumor de Ehrlich. El tumor fue implantado en 30 ratones hembras distribuidas en tres grupos: tratado con PTU, tratado con tiroxina y control. Cada grupo recibió una inyección intraperitoneal de células neoplásicas, pre-incubadas con las soluciones estériles de PTU, tiroxina y agua, respectivamente. En el quinto y séptimo días después de la inoculación, los animales recibieron una inyección intraperitoneal de las soluciones respectivas. En el décimo día después de la inoculación, se sacrificaron los animales. Fueron determinados el volumen de líquido ascítico, el número de células/ml y el porcentaje de células viables. Además se realizaron frotis del líquido ascítico para la evaluación de la citología del tumor. No hubo ninguna diferencia entre los grupos con respecto al volumen del líquido ascítico y el número y viabilidad de las células del tumor. Sin embargo, las células bajo el efecto de la tiroxina presentaron una media significativamente superior del diámetro nuclear, tamaño y número de regiones organizadoras de nucleélos. En este grupo, había un predominio de células claras, redondas con citoplasma abundante, eosinofílico y vacuolado con poca definición de los bordes. Bajo el efecto del PTU, las células del tumor eran pequeñas con el núcleo hipercromático y el mismo número de NORs como el grupo control. Se concluye que el PTU y tiroxina no afectaron el número y viabilidad de las células después de 10 días de inoculación del tumor, pero sí cambiaron las características celulares. Aunque la tiroxina aumenta el tamaño celular y el número de NORs de las celulas del tumor de Ehrlich, PTU causa efectos opuestos.

Papel del infiltrado linfocitario en el hipotiroidismo posquirúrgico de paciente con bocio tóxico difuso preparados con propranolol / Role of lymphocytic infiltration in postsurgical hypothyroidism of patients with diffuse toxic goiter prepared with propranolol

Se presentan los resultados obtenidos con dos tipos de preparaciones prequirúrgicas de pacientes con BTD. Un número recibió sólo propranolol (grupos I, II, III) y otro con propiltiouracilo y lugol (grupo IV). En el grupo I con un remanente igual al del grupo IV, el porcentaje de hipotiroidismo, poco tiempo después de la operación fue superior al del grupo IV. En el grupo II (remanente algo mayor) dicho hipotiroidismo fue similar al del grupo IV. De los factores analizados para tratar de darle una explicación a este fenómeno sólo el grado de infiltración linfocitaria parece haber sido el determinante, pues es mayor en los tiroides de pacientes preparados con propranolol que en aquellos preparados con propiltiouracilo más lugol. Esto puede estar relacionado con la acción que sobre el sistema inmunológico posee el antitiroideo de síntesis y que no tiene el beta bloqueador. La implicación terapéutica de nuestros resultados está dada por la necesidad de dejar un remanente tiroideo algo mayor cuando a los pacientes con bocio tóxico difuso, se les prepara con propranolol

Terapêutica descontínua como fator precipitante de reaçöes adversas ao propiltiouracil / Discontinuous treatment as a precipitant factor of adverse reaction to propylthiouracil

As drogas antitiroidianas sao amplamente prescritas para controle dos estados hipertiroidianos desde 1940. Existem evidências de que as reaçoes adversas ao propiltiouracil (PTU) sao imunologicamente mediadas. A sua utilizaçao é, em geral prolongada e a descontinuidade da terapêutica nao é infrequente. Esta exposiçao repetida ao PTU poderia estar associada a um maior risco de desencadeamento das reaçoes adversas por induzir mecanismo de hipersensibilidade. Estudamos, retrospectivamente 56 pacientes (média de idade = 38,7+ 14,6 anos; 43 femininos e 13 masculinos) com hipertiroidismo tratados com PTU e que tiveram necessidade de internaçao, sendo que 46,4 por cento tiveram o tratamento descontinuado por pelo menos 15 dias. Efeitos adversos ao PTU foram observados em 23,2 por cento dos pacientes estudados. Daqueles com uso descontínuo, 34 por cento apresentaram efeitos adversos, sendo 56 por cento dos casos potencialmente graves (agranulocitose e hepatite), enquanto somente 13,3 por cento daqueles que usaram continuamente a medicaçao (p=OO3) presentaram reaçoes - um caso de anemia aplástica e 3 casos de reaçoes consideradas de menor importância clínica(leucopeniae e "rash" cutâneo). Sugerimos que as reaçoes imunes adversas ao PTU podem ser desencadeadas mais frequentemente em pacientes que fazem uso descontínuo desta medicaçao.

Doenças de graves: uso clínico de drogas antitireoidianas

Os autores sintetizam um pouco da história do emprego dos antitireoidianos na prática clínica, especificamente em relaçäo ao tratamento do hipertireoidismo da doença de Graves, apresentando razöes para seu uso. Na experiência do Instituto de Endocrinologia da Santa Casa do Rio de Janeiro, as taxas de remissäo do hipertireoidismo, 1 ano após a interrupçäo da medicaçäo foram melhores no grupo de doentes que fez uso da medicaçäo por período superior a 1 ano do que naquele de pacientes que receberam a medicaçäo por período inferior a 1 ano (taxas respectivamente de 44,28% e 12,96%). Os antitireoidianos devem continuar sendo empregados como primeira opçäo no tratamento do hipertireoidismo da doença de Graves. Em caso de impossibilidade de controle da doença, deve-se recorrer às formas ablativas de tratamento, uso do lado radioativo ou cirurgia

Nódulo tiroídeo en enfermedad de Basedow Graves y cáncer tiroídeo: experiencia en 6 pacientes / Thyroid nodules in Basedow Graves disease and thyroid cancer: experience in 6 patients

Traditionally, Basedow graves disease was considered a protection against cancer. However, recent reports suggest that cancer occurs with a higher frequency than expected and is more aggressive in this disease. We report six patients with hyperthyroidism due to a Basedow Graves disease that presented a palpable thyroid nodule, which was cold in the scintiscan and solid in the ultrasound examination. Fine needle cytology disclosed cancer in 5 cases (2 with cytological features of greater aggressiveness) and a nodular hyperplasia in one. The diagnosis was confirmed in the surgical piece in all patients. We conclude that Basedow Graves disease and thyroid cancer, which can have an increased aggressiveness, may coexist

Histological study of the thyroids of rats treated with propyl thyouracil, parotidectomyzed and parotidectomyzed treated with propyl thyouracil

Os autores estudaram, histologicamente, as glândulas tireóides de quatro grupos experimentais de ratos: Grupo controle (I), ratos submetidos à extirpaçäo cirúrgica das glândulas parótidas (Grupo II), ratos tratados com 25 mg diários de 6-propil-2-tiouracil (Grupo III) e ratos parotidectomizados e posteriormente tratados com 25 mg diários de 6-propil-2-tiouracil (Grupo IV). Após 26 dias consecutivos de administraçäo de 6-propil-2-tiouracil, todos os animais foram sacrificados. O aspecto histológico da tireóide dos animais tratados com a droga antitireoideana (Grupo III) foi compatível com o de hipofunçäo da glândula. Nos animais parotidectomizados (Grupo II), o aspecto histológico foi o de hiperfunçäo glandular. Nos animais parotidectomizados e tratados com o 6-propil-2-tiouracil (Grupo IV), o aspecto histológico mostrou características intermediárias entre o dos Grupos II e III. Estes resultados sugerem que a parotidectomia atenua a hipofunçäo tireoideana causada pela administraçäo do 6-propil-2-tiouracil, bem como vem enfatizar a hipótese da inter-relaçäo funcional entre glândulas salivares e tireóide